NCT02639598

Brief Summary

Chronic migraine (CM) is a prevalent and devastating disorder with limited therapeutic options. This study explored the efficacy of 10 mg/day flunarizine for CM prophylaxis as compared with 50 mg/day topiramate.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
62

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Jun 2012

Typical duration for phase_4

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2012

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2014

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2015

Completed
10 months until next milestone

First Submitted

Initial submission to the registry

December 16, 2015

Completed
8 days until next milestone

First Posted

Study publicly available on registry

December 24, 2015

Completed
Last Updated

December 24, 2015

Status Verified

December 1, 2015

Enrollment Period

2.5 years

First QC Date

December 16, 2015

Last Update Submit

December 20, 2015

Conditions

Chronic Migraine

Keywords

chronic migraineprophylaxisflunarizinetopiramate

Outcome Measures

Primary Outcomes (2)

  • reduction of total number of headache days (by diary log)

    Patients were followed per 2 weeks at the Headache Clinic. At each visit, diaries were collected, and information within the diary was used for outcome measurement.

    week 7 to 8 after treatment (T4) compared to week -2 to 0 before treatment (T0)

  • reduction of number of migraine days (by diary log)

    Patients were followed per 2 weeks at the Headache Clinic. At each visit, diaries were collected, and information within the diary was used for outcome measurement.

    week 7 to 8 after treatment (T4) compared to week -2 to 0 before treatment (T0)

Secondary Outcomes (3)

  • reduction of number of days of acute abortive medication intake (by diary log)

    week 7 to 8 after treatment (T4) compared to week -2 to 0 before treatment (T0)

  • reduction of number of acute abortive medication tablets taken (by diary log)

    week 7 to 8 after treatment (T4) compared to week -2 to 0 before treatment (T0)

  • fifty percent responder rate (by diary log)

    week 7 to 8 after treatment (T4) compared to week -2 to 0 before treatment (T0)

Study Arms (2)

flunarizine

EXPERIMENTAL

This study consisted of two periods: a prospective baseline screening period lasting up to 2 weeks (week -2 to week 0, T0), and a treatment period lasting 8 weeks after enrollment (weeks 0-8, T1-T4). The treatment phase consisted of a 2-week titration period (T1) and a 6-week maintenance period (T2-T4). During the titration period, subjects were given 5 mg/day flunarizine once daily in the first week, followed by 10 mg/day flunarizine in divided doses (twice daily) in the second week. When subjects could not tolerate this target dose, the initial dose was continued through T4.

Drug: Flunarizine

topiramate

ACTIVE COMPARATOR

This study consisted of two periods: a prospective baseline screening period lasting up to 2 weeks (week -2 to week 0, T0), and a treatment period lasting 8 weeks after enrollment (weeks 0-8, T1-T4). The treatment phase consisted of a 2-week titration period (T1) and a 6-week maintenance period (T2-T4). During the titration period, subjects were given 25 mg/day topiramate once daily in the first week, followed by 50 mg/day topiramate in divided doses (twice daily) in the second week. When subjects could not tolerate this target dose, the initial dose was continued through T4.

Drug: Topiramate

Interventions

FlunarizineDRUG

as in "arm descriptions"

Also known as: sibelium
flunarizine
TopiramateDRUG

as in "arm descriptions"

Also known as: topamax
topiramate

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ICHD-IIR criteria for CM (as reported by the patient)
  • Experienced ≥7 days of headache lasting ≥30 min during T0 (-2 week to 0 week).
  • On ≥4 of these days, subjects were required to have experienced migrainous headache
  • Prophylaxis-naïve (i.e., patients could not receive any preventive medications)
  • With and without medication overuse

You may not qualify if:

  • Headache type other than CM
  • Migraine onset after the age of 50 years
  • CM onset after the age of 60 years
  • Previous history of migraine prophylaxis before enrollment
  • Pregnancy or nursing status
  • History of hepatic or renal disorder, nephrolithiasis or other severe systemic disease
  • Severe depression (BDI score ≥ 30 at visit 1)
  • Conditions incompatible with MRI, such as claustrophobia or metallic or electric implants

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (12)

  • Lewis D, Ashwal S, Hershey A, Hirtz D, Yonker M, Silberstein S; American Academy of Neurology Quality Standards Subcommittee; Practice Committee of the Child Neurology Society. Practice parameter: pharmacological treatment of migraine headache in children and adolescents [RETIRED]: report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society. Neurology. 2004 Dec 28;63(12):2215-24. doi: 10.1212/01.wnl.0000147332.41993.90.

    PMID: 15623677BACKGROUND

  • Evers S, Afra J, Frese A, Goadsby PJ, Linde M, May A, Sandor PS; European Federation of Neurological Societies. EFNS guideline on the drug treatment of migraine--revised report of an EFNS task force. Eur J Neurol. 2009 Sep;16(9):968-81. doi: 10.1111/j.1468-1331.2009.02748.x.

    PMID: 19708964BACKGROUND

  • Pringsheim T, Davenport W, Mackie G, Worthington I, Aube M, Christie SN, Gladstone J, Becker WJ; Canadian Headache Society Prophylactic Guidelines Development Group. Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci. 2012 Mar;39(2 Suppl 2):S1-59.

    PMID: 22683887BACKGROUND

  • Treatment Guideline Subcommittee of the Taiwan Headache Society. [Treatment guidelines for preventive treatment of migraine]. Acta Neurol Taiwan. 2008 Jun;17(2):132-48. Chinese.

    PMID: 18686655BACKGROUND

  • Silvestrini M, Bartolini M, Coccia M, Baruffaldi R, Taffi R, Provinciali L. Topiramate in the treatment of chronic migraine. Cephalalgia. 2003 Oct;23(8):820-4. doi: 10.1046/j.1468-2982.2003.00592.x.

    PMID: 14510929RESULT

  • Bartolini M, Silvestrini M, Taffi R, Lanciotti C, Luconi R, Capecci M, Provinciali L. Efficacy of topiramate and valproate in chronic migraine. Clin Neuropharmacol. 2005 Nov-Dec;28(6):277-9. doi: 10.1097/01.wnf.0000192136.46145.44.

    PMID: 16340383RESULT

  • Diener HC, Bussone G, Van Oene JC, Lahaye M, Schwalen S, Goadsby PJ; TOPMAT-MIG-201(TOP-CHROME) Study Group. Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study. Cephalalgia. 2007 Jul;27(7):814-23. doi: 10.1111/j.1468-2982.2007.01326.x. Epub 2007 Apr 18.

    PMID: 17441971RESULT

  • Silberstein SD, Lipton RB, Dodick DW, Freitag FG, Ramadan N, Mathew N, Brandes JL, Bigal M, Saper J, Ascher S, Jordan DM, Greenberg SJ, Hulihan J; Topiramate Chronic Migraine Study Group. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache. 2007 Feb;47(2):170-80. doi: 10.1111/j.1526-4610.2006.00684.x.

    PMID: 17300356RESULT

  • Silberstein S, Lipton R, Dodick D, Freitag F, Mathew N, Brandes J, Bigal M, Ascher S, Morein J, Wright P, Greenberg S, Hulihan J. Topiramate treatment of chronic migraine: a randomized, placebo-controlled trial of quality of life and other efficacy measures. Headache. 2009 Sep;49(8):1153-62. doi: 10.1111/j.1526-4610.2009.01508.x.

    PMID: 19719543RESULT

  • Martinez-Lage JM. Flunarizine (Sibelium) in the prophylaxis of migraine. An open, long-term, multicenter trial. Cephalalgia. 1988;8 Suppl 8:15-20. doi: 10.1177/03331024880080S804.

    PMID: 3052850RESULT

  • Visudtibhan A, Lusawat A, Chiemchanya S, Visudhiphan P. Flunarizine for prophylactic treatment of childhood migraine. J Med Assoc Thai. 2004 Dec;87(12):1466-70.

    PMID: 15822542RESULT

  • Li HL, Kwan P, Leung H, Yu E, Tsoi TH, Hui AC, Sheng B, Lau KK. Topiramate for migraine prophylaxis among Chinese population. Headache. 2007 Apr;47(4):616-9. doi: 10.1111/j.1526-4610.2007.00763_3.x.

    PMID: 17445114RESULT

MeSH Terms

Interventions

FlunarizineTopiramate

Intervention Hierarchy (Ancestors)

PiperazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFructoseHexosesMonosaccharidesSugarsCarbohydratesKetoses

Study Officials

  • Shuu-Jiun Wang, M.D.

    Taipei Veterans General Hospital, Taiwan

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Deputy Head, Neurological Institute

Study Record Dates

First Submitted

December 16, 2015

First Posted

December 24, 2015

Study Start

June 1, 2012

Primary Completion

December 1, 2014

Study Completion

March 1, 2015

Last Updated

December 24, 2015

Record last verified: 2015-12

Data Sharing

IPD Sharing
Will not share